Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Expert Opin Ther Pat. 2023 Jul-Dec;33(7-8):503-521. doi: 10.1080/13543776.2023.2262136. Epub 2023 Nov 6.
Trk inhibitors are significant in the realm of personalized medicine as they target specific genetic alterations, such as gene fusions, leading to improved treatment outcomes for cancer patients. By tailoring the treatment to the genetic characteristics of the tumor rather than the tumor type, Trk inhibitors offer the potential for more effective and precise therapies, resulting in enhanced response rates and prolonged survival for patients with fusion-positive cancers.
Patents covering type I inhibitors targeting the Trk family are discussed, building upon our prior review series on Trk inhibitors. Relevant patents were identified through the Web of Science database, Google, and Google Patents.
The field of Trk inhibitors has evolved significantly, as reflected in the current patent literature, which emphasizes the selective structural refinement of clinical champions. Efforts now concentrate on enhancing efficacy against on-target resistance mechanisms, with modifications made to improve potency, reduce toxicity, and enhance pharmacokinetics. Combination therapies show potential to address off-target resistance mechanisms and improve treatment outcomes. Challenges remain in accurately diagnosing gene alterations and integrating screening into routine clinical practice. Trk inhibitors have surpassed their conventional role of inhibition and are now seeing new applications in radiopharmaceutical development and as molecular targeting agents.
Trk 抑制剂在个性化医学领域具有重要意义，因为它们针对特定的基因改变，如基因融合，从而改善癌症患者的治疗效果。通过根据肿瘤的遗传特征而不是肿瘤类型来定制治疗方案，Trk 抑制剂为更有效和精确的治疗提供了潜力，从而提高了融合阳性癌症患者的反应率和生存率。
本专利涵盖了针对 Trk 家族的 I 型抑制剂，这是在我们之前关于 Trk 抑制剂的综述系列基础上进行的讨论。通过 Web of Science 数据库、Google 和 Google Patents 确定了相关专利。
Trk 抑制剂领域已经有了显著的发展，这反映在当前的专利文献中，该文献强调了临床冠军的选择性结构细化。目前的努力集中在提高针对靶标耐药机制的疗效上，通过修饰来提高效力、降低毒性和增强药代动力学。联合治疗显示出解决非靶标耐药机制和改善治疗效果的潜力。在准确诊断基因改变和将筛选纳入常规临床实践方面仍然存在挑战。Trk 抑制剂已经超越了其传统的抑制作用，现在在放射性药物开发和作为分子靶向剂方面有了新的应用。
